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The center is named after George M. Low, who was an important administrator at NASA and President of the institute. With the support of Eastman Kodak, IBM, Colt Industries and General Electric, a proposal was made to Governor Hugh Carey to jointly sponsor a research and teaching center to promote industrial innovation. In July 1982, the State of New York agreed to use Rensselaer as the site for the new center. President Low stated that the State had "taken a giant step in its efforts to attract, nurture and keep advanced technology business in the state, a step that is certain to make a substantial impact on New York's economy."[1] Construction began during the summer of 1984 and the center was dedicated on May 14, 1987.

The CII building is notorious for its tall, hollow center stairwells. In 1992 the self-declared Rensselaer Drop Squad spent most of a semester dropping a series of ever more bizarre items down the 7-story stairwell before they were eventually apprehended. The items included typewriters, 150 McDonald's hamburgers, tennis balls and a Christmas tree.[2]

On 29 March 2007, RPI graduate Anson Tripp committed suicide by jumping from the top of one of the stairwells after traveling to RPI from Massachusetts.[3] Because of uncertainties surrounding the death, there was a full evacuation of the building and shutdown of all campus activities after his body was found. In August 2008, metal cables were installed in the center of the two main stairwells to prevent objects from falling, most likely in response to this event.

Starting in early 2008, planning began on an exterior overhaul, replacing the vast network of faulty bricks that encase the building. Black tarp was placed around part of the building to prevent falling bricks from injuring people below. As of February 2011, work on the north wall of the central tower has been completed, with work beginning on the northern annex section of the building.

Upon his death, the Low family bequeathed all of Low's awards and memorabilia to the institute. These possessions were included in the George M. Low Gallery, a museum on the fourth floor, which is a tribute to George Low, NASA, and the engineers of the Apollo program. It is designed to make one feel almost as if they are in outer space; darkness contrasts with the lit exhibits, and pictures of astronauts and space are backlit from the outside..